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The Potency of New Muscle Relaxants on Recombinant Muscle-Type Acetylcholine Receptors

Nigrovic, Vladimir, MD

doi: 10.1097/00000539-200211000-00067
LETTERS TO THE EDITOR: Letters & Announcements
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Department of Anesthesiology

Medical College of Ohio

Toledo, Ohio

To the Editor:

I congratulate Dr. Paul and coworkers on their exciting findings (1). Three questions related to these findings come to mind.

  1. In view of the frequently discussed relationship between the onset of neuromuscular block and potency of muscle relaxants, did the authors observe a dependence of the onset and offset rates of inhibition on the potency of muscle relaxants (defined as IC50 at the ε-nAChR)?
  2. The Hill exponent of around 1 for ε-nAChR (as shown in the authors’ Table 1) is smaller than the exponent in dose-response studies in humans, reported to vary from 4 to 6 (2). Can the authors offer reasons for this difference?
  3. Figure 5 from Dr. Paul and colleagues’ article relates the values of IC50to the ED50values in humans. The correlation might have been more meaningful if IC50 (a concentration) were related to IC50 (also a concentration) for producing neuromuscular block in vitro. Such data are, for example, available for guinea-pig phrenic nerve-diaphragm preparation (3). The correlation is similar to that presented in Figure 5. However, the IC50 values reported by Paul and coworkers (1) are between 30 and 60 times lower than the in vitro IC50 values for neuromuscular block. Is there a reason for this difference?

Vladimir Nigrovic, MD

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References

1. Paul M, Kindler CH, Fokt RM, Dresser MI, Dipps NCJ, Yost CS. The potency of new muscle relaxants on recombinant muscle-type acetylcholine receptors. Anesth Analg 2002; 94: 597–603.
2. Kopman A, Klewicka M, Neuman G. An alternative method for estimating the dose-response relationships of neuromuscular blocking drugs. Anesth Analg 2000; 90: 1191–7.
3. Vizi ES, Lendvai B. Side effects of nondepolarizing muscle relaxants: Relationship to their antinicotinic and antimuscarinic actions. Pharmacol Ther 1997; 73: 75–89.
© 2002 International Anesthesia Research Society